Human class II histocompatibility antigen typing is already of substantial importance in determining disease susceptibility in individuals. Present serologic methods of class II antigen typing are limited by the polyclonal nature of many antisera, by the fact that many of the available human antisera react with multiple different determinants and by the difficulty of obtaining allele specific as compared with species specific murine monoclonal antisera against human DR class II MHC antigens. The present proposal is to develop a procedure that will rapidly make it possible to clone and express composite class II antigens that have single exons from human DC, DR or SB antigens incorporated and substituting for corresponding exons of analogous mouse antigens. These will then be used for immunization procedures to generate mouse monoclonal antibodies, a much larger fraction of which will be allele specific rather than species specific. Therefore, these procedures could lead to the efficient production of a new generation of serologic reagents for human MHC typing that would provide much better resolution than the presently available reagents.